β2 adrenergic receptor agonists are advantageously administered directly into the respiratory tract by inhalation when used for treating pulmonary or respiratory disorders. Several types of pharmaceutical inhalation devices have been developed for administering therapeutic agents by inhalation including dry powder inhalers (DPI), metered-dose inhalers (MDI) and nebulizer inhalers. It is highly desirable to have a crystalline form of the β2 adrenergic receptor agonists that is neither hygroscopic nor deliquescent and which has a relatively high melting point thereby allowing the material to be micronized without significant decomposition or loss of crystallinity to prepare the pharmaceutical compositions and formulations for use in such devices.
5-(2-{[6-(2,2-difluoro-2-phenylethoxy)hexyl]amino}-1-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one is claimed and described in published patent application WO 2006/122788 A1.
Although the 5-(2-{[6-(2,2-difluoro-2-phenylethoxy)hexyl]amino}-1-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one has shown adequate pharmacological behaviour it has proved difficult to obtain it in the form of a salt which is crystalline, not hygroscopic nor deliquescent and which has a relatively high melting point to enable micronization.
So far no crystalline salt of 5-(2-{[6-(2,2-difluoro-2-phenylethoxy)hexyl]amino}-1-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one having the desired properties has been reported.
Accordingly, a need exists for stable, non-deliquescent salt forms of this compound which has acceptable levels of hygroscopicity and relatively high melting points.